The goal of this project is to determine whether deficits in cytosolic free calcium are diagnostic for Alzheimer's disease. Several deficits in calcium is and calcium dependent processed have been described for peripheral tissues from Alzheimer's patients. These include deficits in homeostasis, a decline in protein phosphorylation, reduced growth factor response, depressed cell spreading decreased glucose and glutamine oxidation. The main objective of this proposal is to determined illnesses (e.g., Pick's disease, Parkinson's dementia and multi-infarct dementia). The mechanisms for the decline in cytosolic free calcium in Alzheimer's disease are unclear. The calcium binding proteins play a role in buffering intracellular calcium and studies be designed to determine whether they are altered during Alzheimer's disease. Fibroblasts from individuals who are at risk for developing Alzheimer's disease (e.g., familial Alzheimer's disease) will also be tested to determine whether deficits in cytosolic free calcium appear prior to the clinical signs of the disorder. These approaches will help us to diagnose Alzheimer's disease understand the mechanisms that underlie the degenerative disorder and aid in the design of effective therapeutic strategies.